A novel fracture liaison service using digital health: impact on mortality in hospitalized elderly osteoporotic fracture patients.

We examined the performance of an intelligent fracture liaison service (FLS) assisted by digital health (DH) to reduce all-cause mortality (ACM) risk. According to our findings, the new FLS reduced ACM by 36%. INTRODUCTION: A well-designed secondary prevention program known as FLS enhances the bone densitometry-based assessment rate as well as osteoporosis (OP) medication usage following a fracture. However, there are only a few reports on FLS incorporating DH, and it remains unclear whether this integration has influenced patient ACM, which refers to the overall death rate from any cause during the study period. METHODS: This retrospective observational study was conducted on data from the Fragility Fracture Registration System database linked to the Regional Health Registration Platform of Kunshan City and the Population Death Registration System of Jiangsu Province for one tertiary-level A hospital in China. Patients aged ≥ 50 years, who experienced an OP fracture between January 1, 2017, and July 27, 2022, requiring hospitalization, were selected for analysis. We compared the outcomes of patients who received routine fragility fracture management (the no-FLS group) or FLS (the FLS group). We employed multivariable Cox regression with inverse probability weighting based on the propensity score (PS). RESULTS: Of 2317 patients, 756 (32.6%) received FLS and 1561 (67.4%) did not. Using PS matching, we minimized the baseline characteristic differences between the two groups in the propensity score-matched samples, relative to the unmatched samples. Based on our analysis, the new FLS reduced ACM by 36% (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.47 to 0.87; P-value = 0.004). Moreover, FLS patients experienced further reductions in fall-related mortality, refracture rate, and total refracture-related hospital costs, and had increased dual-energy X-ray absorptiometry (DXA) testing and treatment initiation rates, relative to the no-FLS patients. CONCLUSIONS: A new FLS model implementation assisted by DH can effectively reduce ACM among elderly patients with OP fractures requiring surgery. In future investigations, we recommend examining the scalability of this model.

Sex differences in hemoglobin levels and five-year refracture risk in patients with osteoporotic fractures: a retrospective cohort analysis.

We conducted a retrospective cohort analysis to examine the association between hemoglobin (Hb) levels and refracture risk in elderly patients with osteoporotic fractures (OPFs). Our findings suggest a nonlinear relationship exists in females, and females with Hb levels below 10.7 g/dL may be at a higher risk of refracture. INTRODUCTION: Hematopoiesis and bone health have a reciprocal influence on each other. Nevertheless, there is a scarcity of in-depth research on the association between Hb levels and the occurrence of fractures. The present research aimed to investigate the correlation between Hb levels and the rate of refracture within 5 years among individuals with OPFs. METHODS: A retrospective cohort analysis was undertaken between 2017 and 2022. The study included 1906 individuals who were inhabitants of Kunshan and were over 60 years old. These individuals had experienced an OPF between January 1, 2017, and July 27, 2022, resulting in their hospitalization. Cox proportional hazard regression models were used to evaluate the risk of refracture within 5 years based on the Hb levels acquired during the admission examination, with consideration for sex differences. A nonlinear relationship was identified using smoothed curve fitting and threshold analysis. Kaplan-Meier curves were used to compare refracture rates between patients with low and high Hb levels. RESULTS: Elderly female patients with OPFs and lower Hb levels exhibited a significantly higher risk of a 5-year refracture. Conversely, no significant associations were observed between the two variables in male patients. A nonlinear correlation was found between Hb levels and the probability of refracture in females, with a turning point identified at 10.7 g/dL of Hb levels. A strong negative association was observed with the five-year refracture rate when Hb levels fell below 10.7 g/dL (hazard ratio (HR) = 0.63; 95% confidence interval (CI) 0.48 to 0.83; P-value = 0.0008). This finding suggests that for every 1 g/dL increase in Hb below 10.7 g/dL, the risk of refracture reduced by 37%. However, no statistically significant association was observed when Hb levels were above 10.7 g/dL. CONCLUSIONS: The findings demonstrated a significant negative correlation between Hb levels and the likelihood of refracture in elderly female patients with OPFs and suggested that elderly females with recent OPFs and Hb levels below 10.7 g/dL may be at a higher risk of refracture. Additionally, the Hb levels can serve as an indicator of bone fragility in elderly female patients with OPFs. These findings highlight the importance of monitoring Hb levels as a part of comprehensive management strategies to both assess skeletal health and prevent refractures in this population.

Strategies for the Construction of Benzobicyclo[3.2.1]octane in Natural Product Synthesis.

Benzobicyclo[3.2.1]octane is a cage-like unique motif containing a bicyclo[3.2.1]octane structure fused with at least one benzene ring. It is found in various natural products that exhibit structural complexities and important biological activities. The total synthesis of natural products possessing this challenging structure has received considerable attention, and great advances have been made in this field during the past 15 years. This review summarizes thus far achieved chemical syntheses and synthetic studies of natural compounds featuring the benzobicyclo[3.2.1]octane core. It focuses on strategic approaches constructing the bridged structure, aiming to provide a useful reference for inspiring further advancements in strategies and total syntheses of natural products with such a framework.

Recent progress of iron-based nanomaterials in gene delivery and tumor gene therapy.

Gene therapy aims to modify or manipulate gene expression and change the biological characteristics of living cells to achieve the purpose of treating diseases. The safe, efficient, and stable expression of exogenous genes in cells is crucial for the success of gene therapy, which is closely related to the vectors used in gene therapy. Currently, gene therapy vectors are mainly divided into two categories: viral vectors and non-viral vectors. Viral vectors are widely used due to the advantages of persistent and stable expression, high transfection efficiency, but they also have certain issues such as infectivity, high immunological rejection, randomness of insertion mutation, carcinogenicity, and limited vector capacity. Non-viral vectors have the advantages of non-infectivity, controllable chemical structure, and unlimited vector capacity, but the transfection efficiency is low. With the rapid development of nanotechnology, the unique physicochemical properties of nanomaterials have attracted increasing attention in the field of drug and gene delivery. Among many nanomaterials, iron-based nanomaterials have attracted much attention due to their superior physicochemical properties, such as Fenton reaction, magnetic resonance imaging, magnetothermal therapy, photothermal therapy, gene delivery, magnetically-assisted drug delivery, cell and tissue targeting, and so on. In this paper, the research progress of iron-based nanomaterials in gene delivery and tumor gene therapy is reviewed, and the future application direction of iron-based nanomaterials is further prospected.

Direct Degradation of Fresh and Dried Macroalgae by Agarivorans albus B2Z047.

Marine macroalgae are increasingly recognized for their significant biological and economic potential. The key to unlocking this potential lies in the efficient degradation of all carbohydrates from the macroalgae biomass. However, a variety of polysaccharides (alginate, cellulose, fucoidan, and laminarin), are difficult to degrade simultaneously in a short time. In this study, the brown alga Saccharina japonica was found to be rapidly and thoroughly degraded by the marine bacterium Agarivorans albus B2Z047. This strain harbors a broad spectrum of carbohydrate-active enzymes capable of degrading various polysaccharides, making it uniquely equipped to efficiently break down both fresh and dried kelp, achieving a hydrolysis rate of up to 52%. A transcriptomic analysis elucidated the presence of pivotal enzyme genes implicated in the degradation pathways of alginate, cellulose, fucoidan, and laminarin. This discovery highlights the bacterium's capability for the efficient and comprehensive conversion of kelp biomass, indicating its significant potential in biotechnological applications for macroalgae resource utilization.

Spin-State Control in Dysprosium(III) Metallacrown Magnets via Thioacetal Modification.

Integrating controllable spin states into single-molecule magnets (SMMs) enables precise manipulation of magnetic interactions at a molecular level, but remains a synthetic challenge. Herein, we developed a 3d-4f metallacrown (MC) magnet [DyNi5(quinha)5(Clsal)2(py)8](ClO4) ⋅ 4H2O (H2quinha=quinaldichydroxamic acid, HClsal=5-chlorosalicylaldehyde) wherein a square planar NiII is stabilized by chemical stacking. Thioacetal modification was employed via post-synthetic ligand substitutions and yielded [DyNi5(quinha)5(Clsaldt)2(py)8](ClO4) ⋅ 3H2O (HClsaldt=4-chloro-2-(1,3-dithiolan-2-yl)phenol). Thanks to the additional ligations of thioacetal onto the NiII site, coordination-induced spin state switching (CISSS) took place with spin state altering from low-spin S=0 to high-spin S=1. The synergy of CISSS effect and magnetic interactions results in distinct energy splitting and magnetic dynamics. Magnetic studies indicate prominent enhancement of reversal barrier from 57 cm-1 to 423 cm-1, along with hysteresis opening and an over 200-fold increment in coercive field at 2 K. Ab initio calculations provide deeper insights into the exchange models and rationalize the relaxation/tunnelling pathways. These results demonstrate here provide a fire-new perspective in modulating the magnetization relaxation via the incorporation of controllable spin states and magnetic interactions facilitated by the CISSS approach.

Homochiral Metallacycle Used as a Stationary Phase for Capillary Gas Chromatographic Separation of Chiral and Achiral Compounds.

Metallacycles are a novel class of supramolecular materials with circular structures, internal cavities, and abundant host-guest chemical properties that have exhibited good application prospects in many fields. However, to the best of our knowledge, no research on the use of metallacycles as stationary phases for gas chromatographic (GC) separations has been published yet. In this work, we report for the first time the use of a homochiral metallacycle, [ZnCl2L]2, as a stationary phase for GC separations. [ZnCl2L]2 was synthesized by reaction of (S)-(1-isonicotinoylpyrrolidin-2-yl)methyl-isonicotinate (L) with ZnCl2 via coordination-driven self-assembly. The [ZnCl2L]2-coated column displayed an excellent separation performance not only of organic isomers but also of racemic compounds. Sixteen racemates (including alcohols, esters, amino acid derivatives, ethers, organic acids, and epoxides) and 21 isomeric compounds (including positional, structural, and cis/trans-isomers) were well separated on the [ZnCl2L]2-coated column. Impressively, some racemates were resolved with high resolution values (Rs), including 1,2-butanediol diacetate (Rs = 25.86), ethyl 3-hydroxybutyrate (Rs = 20.97), 1,3-butanediol diacetate (Rs = 18.09), and threonine derivative (Rs = 18.61). Compared with the commercial ß-DEX 120 column for separation of the tested racemates, the [ZnCl2L]2-coated column exhibited good enantioseparation complementarity, enabling separation of some racemates that could not be separated, or were not well resolved, by the ß-DEX 120 column. In addition, many organic mixtures, such as n-alkanes, alkylbenzenes, n-alcohols, and a Grob test mixture, were also well separated on the [ZnCl2L]2-coated column. The column also has good reproducibility and thermal stability on separation. This work not only reveals the great potential of metallacycles for GC separations but also opens up a new application of metallacycles in separation science.

Optimization of physical microenvironment to maintain the quiescence of human induced pluripotent stem cell-derived hepatic stellate cells.

Hepatic stellate cells (HSCs) play a crucial role in liver fibrosis by producing excessive extracellular matrix (ECM) following chronic inflammation. However, studying HSC function has been challenging due to the limited availability of primary human quiescent HSCs (qHSCs) in vitro, and the fact that primary qHSCs quickly activate when cultured on plastic plates. Advances in stem cell technology have allowed for the generation of qHSCs from human induced pluripotent stem cells (hiPSCs) with the potential to provide an unlimited source of cells. However, differentiated quiescent-like HSCs (iqHSCs) also activate spontaneously on conventional plastic plates. In this study, we generated iqHSCs from hiPSCs and developed a culture method to maintain such iqHSCs in a lowly activated state for up to 5 days by optimizing their physical culture microenvironment. We observed that three-dimensional (3D) culture of iqHSCs in soft type 1 collagen hydrogels significantly inhibited their spontaneous activation in vitro while maintaining their ability to convert to activated state. Activation of iqHSC was successfully modeled by stimulating them with the fibrotic cytokine TGFß1. Hence, our culture method can be used to generate HSCs with functions comparable to those in a healthy liver, facilitating the development of accurate in vitro liver models for identifying novel therapeutic agents.

Aliiroseovarius subalbicans sp. nov. and Aliiroseovarius sediminis sp. nov., isolated from marine sediment.

Two novel strains (N1Y82T and N1F302T) were isolated from a marine sediment sample taken from the coastal zone of Weihai, PR China. Cells of the two strains were Gram-strain-negative, catalase-positive, oxidase-positive, non-motile and ovoid- to rod-shaped. Strain N1Y82T grew optimally at 16 °C, pH 7.5 and in the presence of 3.0 % (w/v) NaCl. Strain N1F302T grew optimally at 28 °C, pH 7.0-7.5 and in the presence of 2.0-2.5 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences demonstrated that strains N1Y82T and N1F302T belonged to the genus Aliiroseovarius, and were mostly related to Aliiroseovarius sediminilitoris KCTC 23959T with sequence similarity of 96.5 and 97.1 %, respectively. For these two novel strains, C18 : 1 ω7c was the major fatty acid, ubiquinone 10 was the predominant respiratory quinone, and phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, one unidentified aminolipid and one unidentified phospholipid were the major polar lipids. The DNA G+C contents of strain N1Y82T and N1F302T were 61.3 and 59.0 %, respectively. Consequently, strains N1Y82T and N1F302T are considered to represent two novel species of the genus Aliiroseovarius, for which the names Aliiroseovarius subalbicans sp. nov. and Aliiroseovarius sediminis sp. nov. are proposed. The type strains are N1Y82T (=KCTC 82768T=MCCC 1H00524T) and N1F302T (=KCTC 82412T=MCCC 1H00525T), respectively.

Pontibacterium sinense sp. nov., a nitrate-reducing and thiosulphate-oxidizing bacterium, isolated from coastal sediment.

A novel bacterial strain, N1Y112T, was isolated from coastal sediment collected in Weihai, PR China. This Gram-stain-negative, facultatively anaerobic, motile rod-shaped bacterium exhibited the ability to oxidize thiosulphate to sulphate and reduce nitrate to ammonia through its Sox system and nitrate reduction pathway, respectively. The strain grew at 20-35 °C (optimum, 28 °C), pH 6.0-10.0 (optimum, pH 7.5) and in the presence of 1.0-5.0 % (w/v) NaCl (optimum, 3.0 %). Major fatty acids present in the strain included summed feature 8 (comprising C18 : 1 ω7c and/or C18 : 1 ω6c), summed feature 3 (comprising C16 : 1 ω7c and/or C16 : 1 ω6c) and C16 : 0. Its polar lipid profile consisted of one phosphatidylethanolamine, two unknown aminolipids, one aminophosphoglycolipid, one diphosphatidylglycerol, one phosphatidylglycerol, two unknown phospholipids and two unknown lipids. Strain N1Y112T contained ubiquinone-7 and ubiquinone-8 as isoprenoid quinones, with a genomic G+C content of 50.6 mol%. Based on phylogenetic analysis, strain N1Y112T clustered with Pontibacterium granulatum JCM 30316T being its closest relative at 97.1 % 16S rRNA gene sequence similarity. The average nucleotide identity and digital DNA-DNA hybridization values were 77.1 and 20.7 %, respectively, which suggest significant differences between genomes of N1Y112T and P. granulatum JCM 30316T. Based on the findings from its phenotypic, genotypic and phylogenetic analyses, N1Y112T is considered to represent a novel species of the genus Pontibacterium, for which the name Pontibacterium sinense sp. nov. is proposed. The type strain is N1Y112T (=KCTC 72927T=MCCC 1H00429T).

A novel pillar[3]trianglimine macrocycle with a deep cavity used as a chiral selector to prepare a chiral stationary phase by thiol-ene click reaction for enantioseparation in high-performance liquid chromatography.

A chiral pillar[3]trianglimine (C60 H72 N6 O6 ) with a deep cavity has been developed as a chiral selector and bonded to thiolated silica by thiol-ene click reaction to fabricate a novel chiral stationary phase for enantioseparation in high-performance liquid chromatography. The enantioseparation performance of the fabricated chiral stationary phase has been evaluated by separating various racemic compounds, including alcohols, esters, amines, ketones, amino acids, and epoxides, in both normal-phase and reversed-phase elution modes. In total, 14 and 17 racemates have been effectively separated in these two separation modes, respectively. In comparison with two widely used chiral columns (Chiralcel OD-H and Chiralpak AD-H), our novel chiral stationary phase offered good chiral separation complementarity, separating some of the tested racemates that could not be separated or were only partially separated on these two commercial columns. The influences of analyte mass, mobile phase composition, and column temperature on chiral separation have been investigated. Good repeatability, stability, and column-to-column reproducibility of the chiral stationary phase for enantioseparation have been observed. After the fabricated column had been eluted up to 400 times, the relative standard deviations (n = 5) of resolution (Rs) and retention time of the separated analytes were < 0.39% and < 0.20%, respectively. The relative standard deviations (n = 3) of Rs and retention time for column-to-column reproducibility were < 4.6% and < 5.2%, respectively. This study demonstrated that the new chiral stationary phase has great prospects for chiral separation in high-performance liquid chromatography.

Winogradskyella immobilis sp. nov., an Alginate-Hydrolyzing Bacterium Isolated from the Brown Algae Saccharina japonica.

A novel bacterium, designated E313T, was isolated from brown algae Saccharina japonica in Weihai, China. The strain is a Gram-stain-negative, non-flagellated, non-gliding, aerobic, rod-shaped bacterium that grows optimally at 28 °C with pH levels between 7.0 and 7.5 and in the presence of 2-3% (w/v) NaCl. Phylogenetic analyses based on its 16S rRNA gene sequence placed the strain within the monophyletic cluster of the genus Winogradskyella, exhibiting the highest similarity to Winogradskyella wandonensis KCTC 32579T (96.8%). Genome comparison of strain E313T with W. wandonensis KCTC 32579T and W. thalassocola KCTC 12221T revealed average nucleotide identity (ANI) values of 74.2% and 74.8%, and DNA-DNA hybridization (dDDH) values of 19.0% and 19.5%, respectively, lower than prokaryotic species delineation values. The strain E313T could hydrolyze alginate. A total of 123 carbohydrate-active enzymes were annotated according to the CAZy database. Especially, one oligo-alginate lyase and one poly(ß-D-mannuronate) lyase were identified in the genome of strain E313T. Strain E313T possessed MK-6 quinone and iso-C15:0, iso-C15:1 G, iso-C17:0 3-OH, and iso-C15:0 3-OH as main fatty acids. Its major polar lipids were phosphatidylethanolamine (PE), one unidentified aminolipid, and two unknown lipids. Thus, based on phylogenetic, physiological, and chemotaxonomic analyses, we propose a novel species of the genus Winogradskyella, named Winogradskyella immobilis sp. nov., with E313T (= MCCC 1H00506T = KCTC 82731T) as the type strain.

Association between lumbar endplate damage and bone mineral density in patients with degenerative disc disease.

BACKGROUND: To explore the independent association between lumbar endplate damage and bone mineral density (BMD) in patients with degenerative disc disease (DDD). METHODS: This retrospective investigation was based out of a prospectively collected database from the Affiliated Kunshan Hospital of Jiangsu University. Data from 192 DDD patients, collected between December 2018 and January 2022, were chosen for the final analysis. The average total endplate score (TEPS) of lumbar(L) 1-L4 was assessed by magnetic resonance imaging (MRI), and represents the extent of endplate damage. Osteoporosis severity was assessed via the L1-L4 BMD evidenced by dual-energy x-ray absorptiometry (DXA). Other analyzed information included gender, age, body mass index (BMI), and osteophyte score (OSTS). Uni- and multivariate linear regression analyses were employed to evaluate the association between average TEPS and BMD of L1-L4. Moreover, the generalized additive model (GAM) was employed for non-linear association analysis. RESULTS: Upon gender, age, BMI, and OSTS adjustments, a strong independent inverse relationship was observed between average TEPS and BMD (ß, -0.021; 95% CI, -0.035 to -0.007, P-value = 0.00449). In addition, the gender stratification analysis revealed a linear relationship in males, and a non-linear relationship in females. Specifically, there was a significantly stronger negative relationship between average TEPS and BMD in females, when the average TEPS was < 3.75 (ß, -0.063; 95% CI, -0.114 to -0.013; P-value = 0.0157). However, at an average TEPS > 3.75, the relationship did not reach significance (ß, 0.007; 95% CI, -0.012 to 0.027; P-value = 0.4592). CONCLUSIONS: This study demonstrated the independent negative association between average TEPS and BMD values of L1-L4. Upon gender stratification, a linear relationship was observed in males, and a non-linear association in females. The findings reveal that patients with osteoporosis or endplate damage require more detailed examinations and treatment regimen.

Association between serum uric acid levels and bone mineral density in patients with osteoporosis: a cross-sectional study.

BACKGROUND: The results of studies exploring the association between serum uric acid (SUA) and bone mineral density (BMD) have been controversial and inconsistent. We thus sought to explore whether SUA levels were independently associated with BMD in patients with osteoporosis (OP). METHODS: This cross-sectional analysis was conducted using prospectively obtained data from the Affiliated Kunshan Hospital of Jiangsu University database pertaining to 1,249 OP patients that were hospitalized from January 2015 - March 2022. BMD was the outcome variable for this study, while baseline SUA levels were the exposure variable. Analyses were adjusted for a range of covariates including age, gender, body mass index (BMI) and a range of other baseline laboratory and clinical findings. RESULTS: SUA levels and BMD were independently positively associated with one another in OP patients. Following adjustment for age, gender, BMI, blood urae nitrogen (BUN), and 25(OH)D levels, a 0.0286 g/cm2 (ß, 0.0286; 95% confidence interval [CI], 0.0193-0.0378, P < 0.000001) increase in BMD was observed per 100 µmol/L rise in SUA levels. A non-linear association between SUA and BMD was also observed for patients with a BMI < 24 kg/m2, with a SUA level inflection point at 296 µmol/L in the adjusted smoothed curve. CONCLUSIONS: These analyses revealed SUA levels to be independently positively associated with BMD in OP patients, with an additional non-linear relationship between these two variables being evident for individuals of normal or low body weight. This suggests that SUA levels may exert a protective effect on BMD at concentrations below 296 µmol/L in normal- and low-weight OP patients, whereas SUA levels above this concentration were unrelated to BMD.

Association between perioperative blood transfusion and length of hospital stay in patients with osteoporotic fractures.

BACKGROUND: Few studies have examined the relationship between perioperative blood transfusion (PBT) and length of hospital stay (LOS) in patients with osteoporotic fractures. This research aims to study the association between PBT and LOS. METHODS: This is a retrospective cross-sectional study from the Affiliated Kunshan Hospital of Jiangsu University, Suzhou, China, involving 2357 osteoporotic fractures (OPF) patients who received surgical treatment during hospitalization from January 2017 and March 2022. Multiple linear regression was used to analyze the relationship between PBT and LOS. In the analysis, PBT volume was the dependent variable, whereas LOS was the independent variable. Simultaneously, age, gender, body mass index, hemoglobin, primary diagnosis, American Society of Anesthesiologists, creatinine (Cr), anesthesia, surgical method, and Charlson comorbidity index were included as covariates. The generalized additive model was then used to study nonlinear associations. Two piecewise linear regression exemplary evaluated the inception results for smoothing the curve. RESULTS: Our results proved that PBT was positively correlated with LOS in the fully adjusted model (ß, 0.21; 95% CI, 0.04 to 0.37; P < 0.0001). Furthermore, a "U-shape" nonlinear relationship existed between PBT and LOS. When the concentration of PBT was between 0 and 1.5 units, it was manifested as a negative correlation between PBT and LOS. However, there was a positive association between PBT and LOS when PBT levels exceeded 1.5 units. CONCLUSIONS: This study demonstrated that PBT and LOS in the OPF population were independent with a nonlinear relationship. These results suggest that PBT may be protective for patients with long LOS. If these findings are confirmed, the LOS in OPF patients can be regulated through appropriate perioperative blood transfusion.

Three-Step Synthesis of the Antiepileptic Drug Candidate Pynegabine.

Pynegabine, an antiepileptic drug candidate in phase I clinical trials, is a structural analog of the marketed drug retigabine with improved chemical stability, strong efficacy, and a better safety margin. The reported shortest synthetic route for pynegabine contains six steps and involves the manipulation of highly toxic methyl chloroformate and dangerous hydrogen gas. To improve the feasibility of drug production, we developed a concise, three-step process using unconventional methoxycarbonylation and highly efficient Buchwald-Hartwig cross coupling. The new synthetic route generated pynegabine at the decagram scale without column chromatographic purification and avoided the dangerous manipulation of hazardous reagents.

Preparation of Chiral Porous Organic Cage Clicked Chiral Stationary Phase for HPLC Enantioseparation.

Porous organic cages (POCs) are a new subclass of porous materials, which are constructed from discrete cage molecules with permanent cavities via weak intermolecular forces. In this study, a novel chiral stationary phase (CSP) has been prepared by chemically binding a [4 + 6]-type chiral POC (C120H96N12O4) with thiol-functionalized silica gel using a thiol-ene click reaction and applied to HPLC separations. The column packed with this CSP presented good separation capability for chiral compounds and positional isomers. Thirteen racemates have been enantioseparated on this column, including alcohols, diols, ketones, amines, epoxides, and organic acids. Upon comparison with a previously reported chiral POC NC1-R-based column, commercial Chiralpak AD-H, and Chiralcel OD-H columns, this column is complementary to these three columns in terms of its enantiomeric separation; and can also separate some racemic compounds that cannot be separated by the three columns. In addition, eight positional isomers (iodoaniline, bromoaniline, chloroaniline, dibromobenzene, dichlorobenzene, toluidine, nitrobromobenzene, and nitroaniline) have also been separated. The influences of the injection weight and column temperature on separation have been explored. After the column has undergone multiple injections, the relative standard deviations (RSDs) for the retention time and selectivity were below 1.0 and 1.5%, respectively, indicating the good reproducibility and stability of the column for separation. This work demonstrates that POCs are promising materials for HPLC separation.

Asymmetric Total Synthesis of Naphthospironone A.

Naphthospironone A, a polyhydroxy cagelike bioactive natural product, was synthesised for the first time in this study. The spiro[bicyclo[3.2.1]octane-pyran] core was constructed by an acid-promoted epoxide-opening lactonisation and a base-induced intramolecular aldol-type cyclisation.

Predicting the acute-phase response fever risk in bisphosphonate-naive osteoporotic patients receiving their first dose of zoledronate.

INTRODUCTION: To devise a precise and efficient tool for predicting the individualized risk of acute-phase response (APR) in bisphosphonate (BP)-naive osteoporotic (OP) patients, receiving their first intravenous dose of zoledronate (ZOL). METHODS: The baseline clinical and laboratory data of 475 consecutive BP-naive OP patients, who received their first intravenous dose of ZOL between March 2016 and March 2021 in the Affiliated Kunshan Hospital of Jiangsu University, were chosen for analysis. Univariate and multivariable logistic regression models were generated to establish candidate predictors of APR fever risk, using three distinct fever thresholds, namely, 37.3 °C (model A), 38.0 °C (model B), and 38.5 °C (model C). Next, using predictor regression coefficients, three fever-threshold nomograms were developed. Discrimination, calibration, and clinical usefulness of each predicting models were then assessed using the area under the curve (AUC), calibration curve (CC), and decision curve analysis (DCA). The internal and external model validations were then performed. RESULTS: The stable predictors were age, serum 25-hydroxy vitamin D, serum total calcium, and peripheral blood erythrocytes count. These were negatively associated with the APR fever risk. The AUCs of models A, B, and C were 0.828 (95% confidence intervals [CI], 0.782 to 0.874), 0.825 (95% CI, 0.767 to 0.883), and 0.879 (95% CI, 0.824 to 0.934), respectively. Good agreement was observed between the predictions and observations in the CCs of all three nomograms. CONCLUSIONS: This study developed and validated nomogram prediction models that can predict APR fever risk in BP-naive OP patients receiving their first infusion of ZOL.

Pseudohalioglobus sediminis sp. nov., isolated from coastal sediment.

A Gram-stain-negative, strictly aerobic, non-motile and rod-shaped bacterial strain, designated NY5T, was isolated from marine sediment collected from coastal area in Weihai, China (122°07' 38.80'' E, 37°33' 57.60'' N). Cells of strain NY5T were 0.6-0.7 µm width and 1.9-2.0 µm length, catalase-positive and oxidase-positive. Growth of NY5T was observed at 25-37 °C (optimum, 28 °C) and pH 6.5-9.5 (optimum, pH 7.5-8.0) and in the presence of 0.5-7.0% (w/v) NaCl (optimum, 2.0%). The isoprenoid quinone was Q-8 and the predominant fatty acids were summed feature 8 (C18:1 ω7c and/or C18:1 ω6c), summed feature 3 (C16:1 ω7c and/or C16:1 ω6c) and C17:1 ω8c. Diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol were the major polar lipids. The DNA G+C content of strain NY5T was 60.1%. Strain NY5T showed the highest 16S rRNA gene sequence similarity (98.2%) with Pseudohalioglobus lutimaris followed by Parahaliea aestuarii (96.9%), Parahaliea maris (96.7%), Parahaliea mediterranea (95.9%), and Halioglobus japonicus (94.9%). Given these phenotypic and chemotaxonomic properties and phylogenetic analyses, strain NY5T was considered to represent a novel species of the genus Pseudohalioglobus, for which the name Pseudohalioglobus sediminis sp. nov. is proposed. The type strain is NY5T (=KCTC 72416T=MCCC 1H00401T).